Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle

Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Química Biológica A; Argentina.

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Detalles Bibliográficos
Autores principales: Centeno, Viviana Andrea, Sato, AY., Cregor, M., Akel, NS., Bellido, T.
Formato: conferenceObject
Lenguaje:Inglés
Publicado: 2023
Materias:
BMD
Acceso en línea:http://hdl.handle.net/11086/550009
Aporte de:
id I10-R141-11086-550009
record_format dspace
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-141
collection Repositorio Digital Universitario (UNC)
language Inglés
topic glucocorticoids
vitamin D
BMD
VDR cKO
spellingShingle glucocorticoids
vitamin D
BMD
VDR cKO
Centeno, Viviana Andrea
Sato, AY.
Cregor, M.
Akel, NS.
Bellido, T.
Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle
topic_facet glucocorticoids
vitamin D
BMD
VDR cKO
description Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Química Biológica A; Argentina.
format conferenceObject
author Centeno, Viviana Andrea
Sato, AY.
Cregor, M.
Akel, NS.
Bellido, T.
author_facet Centeno, Viviana Andrea
Sato, AY.
Cregor, M.
Akel, NS.
Bellido, T.
author_sort Centeno, Viviana Andrea
title Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle
title_short Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle
title_full Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle
title_fullStr Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle
title_full_unstemmed Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle
title_sort vitamin d3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires vdr signaling only in skeletal muscle
publishDate 2023
url http://hdl.handle.net/11086/550009
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AT cregorm vitamind3protectsagainstglucocorticoidinducedmuscleweaknessandbonelossthroughamechanismthatrequiresvdrsignalingonlyinskeletalmuscle
AT akelns vitamind3protectsagainstglucocorticoidinducedmuscleweaknessandbonelossthroughamechanismthatrequiresvdrsignalingonlyinskeletalmuscle
AT bellidot vitamind3protectsagainstglucocorticoidinducedmuscleweaknessandbonelossthroughamechanismthatrequiresvdrsignalingonlyinskeletalmuscle
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spelling I10-R141-11086-5500092024-07-29T20:21:26Z Vitamin D3 protects against glucocorticoid-induced muscle weakness and bone loss through a mechanism that requires VDR signaling only in skeletal muscle Centeno, Viviana Andrea Sato, AY. Cregor, M. Akel, NS. Bellido, T. glucocorticoids vitamin D BMD VDR cKO Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Química Biológica A; Argentina. Fil: Sato, AY. Indiana University School of Medicine. Department of Anatomy & Cell Biology: United States. Fil: Cregor, M. Indiana University School of Medicine. Department of Anatomy & Cell Biology: United States. Fil: Akel, NS. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States. Fil: Bellido, T.. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States. Fil: Bellido, T.. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States. Vitamin D3 has beneficial effects in skeletal muscle and can prevent falls leading to reduced bone fracture risk. Earlier findings showed that administration of 1,25-dihydroxyvitamin D3 (1,25D3) prevents muscle atrophy induced by glucocorticoids (GC) in mice. However, it remains unknown whether these effects are due to direct actions of the hormone in muscle. To answer this question, we generated a mouse model of inducible, skeletal muscle-specific deletion of the Vitamin D3 receptor (VDR) in mature mice. VDRf/f;human skeletal muscle α-actin (HSA)-Cre+/- and littermate control VDRf/f;HSA-Cre-/- mice (C) were treated with tamoxifen (2mg/d 1x/d for 5d) at 3mo of age. At 4mo, mice were implanted with slow-release pellets with 2.1mg/kg/d prednisolone or placebo and were treated with 50ng/kg/d 1,25D3 or vehicle 5x/wk for 4wks, N=13-21. Mice were fed a regular Vitamin D3-containing diet and maintained in a 12h light/dark cycle. The excised VDR form was detected only in skeletal muscle (plantaris and tibialis anterior, TA), but not in kidney, intestine, or bone (other target tissues), nor in any tissues from C mice. Adult-onset deletion of the VDR in muscle did not change body weight, lean body mass, skeletal muscle weight (TA, soleus), or in vivo muscle strength (plantarflexion torque testing), as no differences were detected between VDRf/f;HSA-Cre+/- vs C mice receiving placebo/vehicle or placebo/1,25D3. GC did not alter body weight or lean body mass, but it decreased TA weight and in vivo muscle strength to a similar extent in VDRf/f;HSA-Cre+/- and C mice. These indexes of muscle atrophy induced by GC were prevented by 1,25D3 only in C but not in VDRf/f;HSA-Cre+/- mice. These findings demonstrate that VDR signaling is dispensable for physiological muscle function in vitamin D replete animals, but it is required for the prevention of GC-induced muscle atrophy by 1,25D3. Because of the postulated crosstalk between muscle and bone and our previous findings showing that 1,25D3 also prevents GC-induced bone loss, we examined next whether the response to Vitamin D3 in bone was impacted by the loss of VDR in skeletal muscle. Remarkably, whereas 1,25D3 prevented the decrease in total BMD induced by GC in C mice, 1,25D3 did not prevent the bone loss in VDRf/f;HSA-Cre+/- mice. Taking together, these findings suggest that VDR signaling in skeletal muscle confers protective actions against GC-induced atrophy not only in skeletal muscle, but also in bone. Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Química Biológica A; Argentina. Fil: Sato, AY. Indiana University School of Medicine. Department of Anatomy & Cell Biology: United States. Fil: Cregor, M. Indiana University School of Medicine. Department of Anatomy & Cell Biology: United States. Fil: Akel, NS. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States. Fil: Bellido, T.. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States. Fil: Bellido, T.. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States. Bioquímica y Biología Molecular (ídem 1.6.3) 2023-11-28T14:13:18Z 2023-11-28T14:13:18Z 2022 conferenceObject 1523-4681 http://hdl.handle.net/11086/550009 eng Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0/ Impreso